MicroRNA-137 Is a Novel Hypoxia-responsive MicroRNA That Inhibits Mitophagy via Regulation of Two Mitophagy Receptors FUNDC1 and NIX
Open accessAbstract
Mitophagy receptors mediate the selective recognition and targeting of damaged mitochondria by autophagosomes. The mechanism for the regulation of these receptors remains unknown. Here, we demonstrated that a novel hypoxia-responsive microRNA, microRNA-137 (miR-137), markedly inhibits mitochondrial degradation by autophagy without affecting global autophagy. miR-137 targets the expression of two mitophagy receptors NIX and FUNDC1. Impaired mitophagy in response to hypoxia caused by miR-137 is reversed by re-expression of FUNDC1 and NIX expression vectors lacking the miR-137 recognition sites at their 3' UTR. Conversely, miR-137 also suppresses the mitophagy induced by fundc1 (CDS+3'UTR) but not fundc1 (CDS) overexpression. Finally, we found that miR-137 inhibits mitophagy by reducing the expression of the mitophagy receptor thereby leads to inadequate interaction between mitophagy receptor and LC3. Our results demonstrated the regulatory role of miRNA to mitophagy receptors and revealed a novel link between miR-137 and mitophagy.
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miR-137 inhibits mitophagy by targeting FUNC1 and NIX.
“For example, miR-137 inhibits mitophagy by targeting FUNC1 and NIX [47].”
From miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1) (2016) · cites this paper as [47]
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- Authors
- Li, W., Zhang, X., Zhuang, H., Chen, H.-G., Chen, Y., Tian, W., Wu, W., Li, Y., Wang, S., Zhang, L., Chen, Y., Li, L., Zhao, B., Sui, S., Hu, Z., & Feng, D.
- Affiliations
- Guangdong Medical College (CN)
- Tsinghua University (CN)
- Corresponding author
- Hu, Zhe
- Feng, Du
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 289
- Issue
- 15
- Pages
- 10691-10701
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4036186
- OpenAlex
- W1969728632
- Cited by
- 145
- References
- 55
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 9 · 2023: 7 · 2022: 15 · 2021: 23 · 2020: 16 · 2019: 6 · 2018: 14 · 2017: 15 · 2016: 10 · 2015: 11 · 2014: 4
- FWCI
- 10.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- microRNA-137, mitophagy, hypoxia, FUNDC1, Nix, mitophagy receptors, LC3, 3' UTR regulation, mitochondrial degradation, autophagy
- MeSH terms
- Animals, Autophagy, Fibroblasts, Gene Expression Regulation, Genetic Vectors, HeLa Cells, Humans, Membrane Proteins, Mice, Inbred C57BL, Mitochondria, Phagosomes, Cell Hypoxia, 3' Untranslated Regions, Mitochondrial Proteins, MicroRNAs, Mice, HEK293 Cells
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